dbSNP rs2307466: EIF2AK2:c.-183-148C>G (chr2-37149171-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001135651.3(EIF2AK2):c.-183-148C>G variant causes a intron change. The variant allele was found at a frequency of 0.0595 in 1,028,280 control chromosomes in the GnomAD database, including 2,119 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.047 ( 242 hom., cov: 32)

Exomes 𝑓: 0.062 ( 1877 hom. )

Consequence

EIF2AK2
NM_001135651.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.96

Publications

14 publications found

Variant links:

Genes affected

EIF2AK2 (HGNC:9437): (eukaryotic translation initiation factor 2 alpha kinase 2) The protein encoded by this gene is a serine/threonine protein kinase that is activated by autophosphorylation after binding to dsRNA. The activated form of the encoded protein can phosphorylate translation initiation factor EIF2S1, which in turn inhibits protein synthesis. This protein is also activated by manganese ions and heparin. The encoded protein plays an important role in the innate immune response against multiple DNA and RNA viruses. [provided by RefSeq, Jul 2021]

EIF2AK2 links:

ARL14EPP1 (HGNC:54676): (ARL14EP pseudogene 1)

ARL14EPP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2AK2	NM_001135651.3 link	c.-183-148C>G		intron_variant	Intron 1 of 16	ENST00000233057.9	NP_001129123.1	P19525-1Q8IW76

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2AK2	ENST00000233057.9 link	c.-183-148C>G		intron_variant	Intron 1 of 16	2	NM_001135651.3	ENSP00000233057.4		P19525-1

Frequencies

GnomAD3 genomes

AF:

0.0468

AC:

7123

AN:

152130

Hom.:

238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.0921

Gnomad AMR

AF:

0.0689

Gnomad ASJ

AF:

0.0465

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.0941

Gnomad FIN

AF:

0.0381

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0629

Gnomad OTH

AF:

0.0483

GnomAD4 exome

AF:

0.0617

AC:

54055

AN:

876030

Hom.:

1877

Cov.:

AF XY:

0.0634

AC XY:

29178

AN XY:

460048

show subpopulations

African (AFR)

AF:

0.00977

AC:

217

AN:

22200

American (AMR)

AF:

0.0799

AC:

3482

AN:

43596

Ashkenazi Jewish (ASJ)

AF:

0.0480

AC:

1070

AN:

22278

East Asian (EAS)

AF:

0.0121

AC:

449

AN:

36956

South Asian (SAS)

AF:

0.103

AC:

7638

AN:

74310

European-Finnish (FIN)

AF:

0.0479

AC:

2505

AN:

52340

Middle Eastern (MID)

AF:

0.0718

AC:

328

AN:

4570

European-Non Finnish (NFE)

AF:

0.0621

AC:

35981

AN:

579240

Other (OTH)

AF:

0.0588

AC:

2385

AN:

40540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

2308

4615

6923

9230

11538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

888

1776

2664

3552

4440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0469

AC:

7137

AN:

152250

Hom.:

242

Cov.:

AF XY:

0.0476

AC XY:

3541

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0119

AC:

493

AN:

41554

American (AMR)

AF:

0.0691

AC:

1057

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0465

AC:

161

AN:

3466

East Asian (EAS)

AF:

0.0158

AC:

AN:

5178

South Asian (SAS)

AF:

0.0946

AC:

456

AN:

4822

European-Finnish (FIN)

AF:

0.0381

AC:

404

AN:

10606

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0629

AC:

4276

AN:

68010

Other (OTH)

AF:

0.0511

AC:

108

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

338

677

1015

1354

1692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0579

Hom.:

Bravo

AF:

0.0460

Asia WGS

AF:

0.0590

AC:

206

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

4.0

PromoterAI

0.020

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over